Cancer Biomarkers - Volume 24, issue 3

Authors: Cao, Xiao-Ming

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the role of miR-337-3p targeting Rap1A in modulating proliferation, invasion, migration and apoptosis of cervical cancer cells. METHODS: The expression levels of miR-337-3p and Rap1A in cervical cancer tissues and normal tissues were evaluated through quantitative Real-time PCR (qRT-PCR) and Western blotting; and correlations of miR-337-3p with clinicopathological characteristics and prognosis of patients were also analyzed. Besides, human cervical cancer cell line HeLa cells were randomly divided into five groups (Mock, NC, miR-337-3p mimic, Rap1A, and miR-337-3p mimic + Rap1A groups). CCK-8 assay was utilized to measure cell proliferation, flow cytometry to …evaluate cell apoptosis, and wound-healing and Transwell assays to detect cell migration and invasion. RESULTS: Cervical cancer tissues presented a significant decrease in miR-337-3p and a remarkable increase in Rap1A protein. Besides, the expression levels of miR-337-3p and Rap1A were closely related to the major clinicopathological characteristics of cervical cancer; and patients with high-miR-337-3p-expression had the higher 5-year survival rate (all p < 0.05). When compared to Mock group, cells in miR-337-3p mimic group were suppressed in proliferation, migration, and invasion, but significantly promoted in apoptosis; meanwhile, cells in the Rap1A group showed changes in a completely opposite trend (all p < 0.05). Moreover, Rap1A can reverse the effect of miR-337-3p mimic on cell proliferation, invasion, migration and apoptosis (all p < 0.05). CONCLUSION: MiR-337-3p was discovered to be decreased in cervical cancer, and miR-337-3p up-regulation may inhibit the proliferation, migration and invasion and promote the apoptosis of cervical cancer cells via down-regulating Rap1A. Show more

Keywords: MiR-337-3p, Rap1A, cervical cancer, proliferation, invasion, migration, apoptosis

DOI: 10.3233/CBM-181225

Citation: Cancer Biomarkers, vol. 24, no. 3, pp. 257-267, 2019

Authors: Du, Shanmei | Hu, Wei | Zhao, Yi | Zhou, Hengzhong | Wen, Wei | Xu, Miao | Zhao, Peiqing | Liu, Kui

Article Type: Research Article

Abstract: Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts that play important roles in tumorigenesis and tumor progression. Our study aimed to explore the role of lncRNA MAGI2-AS3 in breast cancer metastatic progression. In the present study, our results showed that MAGI2-AS3 can inhibit the migration and invasion of breast cancer cells. In addition, an increase in MAGI2-AS3 can inhibit microRNA-374a (miR-374a) expression in breast cancer cells. Bioinformatic analysis predicted the correlation between MAGI2-AS3 and miR-374a. Phosphatase and tensin homolog (PTEN) was found to be an novel mRNA target of miR-374a. MAGI2-AS3 upregulation inhibited breast cancer metastatic progression by decreasing miR-374a and …enhancing PTEN expression. Together, our data revealed that lncRNA MAGI2-AS3 is involved in breast cancer cell progression by regulating the miR-374a-PTEN axis. These findings offer new insight into treatment strategies for breast cancer. Show more

Keywords: lncRNA MAGI2-AS3, breast cancer, migration, invasion, miR-374a, PTEN

DOI: 10.3233/CBM-182216

Citation: Cancer Biomarkers, vol. 24, no. 3, pp. 269-277, 2019

Authors: Yuan, Jie | Su, Zhangyao | Gu, Wenchao | Shen, Xianjuan | Zhao, Qiumin | Shi, Linying | Jin, Chunjing | Wang, Xudong | Cong, Hui | Ju, Shaoqing

Article Type: Research Article

Abstract: Multiple myeloma (MM) is a common hematological malignancy that is often associated with osteolytic lesions, anemia and renal impairment. Deregulation of miRNA has been implicated in the pathogenesis of MM. It was found in our study that miR-19b and miR-20a as members of crucial oncogene miR-17-92 cluster were differentially expressed between patients with MM and normal controls by genechip microarray, and this result was further confirmed in sera of patients with MM by qRT-PCR. The functional effect of miR-19b/20a was analyzed and results showed that miR-19b/20a promoted cell proliferation and migration, inhibited cell apoptosis and altered cell cycle in MM …cells. PTEN protein expression was reduced after transfection of miR-19b/20a, suggesting that PTEN was a direct target of miR-19b/20a. In addition, over-expression of miR-19b/20a reversed the anti-proliferation and pro-apoptosis effect of PTEN in MM cells. Finally, our in vivo experiment demonstrated that lentivirus-mediated delivery of miR-20a promoted tumor growth in murine xenograft model of MM, which provide evidence that miR-20a inhibitor exerts therapeutic activity in preclinical models and supports a framework for the development of miR-19b/20a-based treatment strategies for MM patients. Show more

Keywords: Multiple myeloma, miR-19b, miR-20a, PTEN

DOI: 10.3233/CBM-182182

Citation: Cancer Biomarkers, vol. 24, no. 3, pp. 279-289, 2019

Authors: Sahami-Fard, Mohammad Hossein | Kheirandish, Shahnaz | Sheikhha, Mohammad Hasan

Article Type: Research Article

Abstract: BACKGROUND: Colorectal cancer (CRC) is one of the most prevalent cancers and microRNAs are involved in colorectal carcinogenesis and progression. The role of our candidate microRNAs (miR-143-3p, -424-5p, -212-3p and -34a-3p) have been investigated in various cancers. OBJECTIVE: The aim of the current study was to evaluate expression levels of microRNAs (miR-143-3p, -424-5p, -212-3p and -34a-3p) in the sera of patients with CRC in order to identify potential non-invasive biomarker for CRC and investigate the relationship between their expression and clinicopathological features of CRC. METHODS: The serological expression of candidate microRNAs were measured …in 124 participants, including 62 CRC patients and 62 healthy controls and the serum expression levels of candidate miRNAs were quantified by stemloop reverse transcriptionquantitative polymerase chain reaction. RESULTS: In the present study, results showed a significant upregulation expression level of miR-424-5p (P < 0.001) and decreased expression level of miR143-3p was observed in the sera of patients with CRC (P < 0.001). Receiver operating characteristic (ROC) curve analysis demonstrated the area of miR-424-5p and miR-143-3p under the ROC curve for CRC diagnosis were 0.703 and 0.724 respectively (P < 0.001). In addition, down expression of miR-143-3p was significantly associated with tumor size (P = 0.005) and lymph node metastasis (P = 0.020) in CRC patients. CONCLUSIONS: The present investigation suggested that low expression of miR-143-3p and increasing level of miR-424-5p in CRC patients may play an important role in development of CRC and they could function as potential non-invasive biomarkers for CRC. Show more

Keywords: Colorectal cancer, microRNAs, serum, biomarker

DOI: 10.3233/CBM-182171

Citation: Cancer Biomarkers, vol. 24, no. 3, pp. 291-297, 2019

Authors: Sun, Yi | Yang, Bin | Lin, Maosong | Yu, Hong | Chen, Hui | Zhang, Zhenyu

Article Type: Research Article

Abstract: BACKGROUND: Circulating microRNAs (miRNAs) have become increasingly appreciated in the diagnosis and prognosis of colorectal cancer (CRC). OBJECTIVE: The aim of this study was to assess the potential diagnostic and prognostic significance of serum miR-30a-5p as a potential biomarker. METHODS: The expression levels of serum miR-30a-5p were measured in 138 cases with CRC, 50 cases with benign lesions (colorectal adenoma and polyps) and 60 healthy volunteers by quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: The results showed that serum miR-30a-5p levels were frequently downregulated in patients with CRC and benign lesions …in comparison with normal controls. Moreover, serum miR-30a-5p levels in early-stage CRC patients were significantly increased after surgery. Receiver-operating characteristic (ROC) curve analysis demonstrated serum miR-30a-5p could well distinguish CRC patients, early-stage CRC patients from healthy controls with a relative high value of area under the curve (AUC). Furthermore, low serum miR-30a-5p expression was more frequently occurred in CRC patients with aggressive clinical variables. Additionally, CRC patients exhibiting high serum miR-30a-5p expression had significantly prolonged overall survival than those exhibiting low expression. Finally, both univariate and multivariate analyses revealed that serum miR-30a-5p expression was an independent prognostic factor for overall survival in CRC patients. CONCLUSIONS: Collectively, these findings suggested serum miR-30a-5p might act as a novel biomarker for the diagnosis and prognosis of CRC. Show more

Keywords: miR-30a-5p, colorectal cancer, prognosis, diagnosis

DOI: 10.3233/CBM-182129

Citation: Cancer Biomarkers, vol. 24, no. 3, pp. 299-305, 2019

Authors: Zuo, Xiaomin | Kong, Weihao | Feng, Linfei | Zhang, Huabing | Meng, Xiangling | Chen, Wei

Article Type: Research Article

Abstract: BACKGROUND: Previous studies have demonstrated that platelets play an important role in growth, invasion, and angiogenesis of a variety of tumors. Nevertheless, the prognostic role of platelet indices in hepatocellular carcinoma (HCC) has not been explored. The aim of this study was to explore the association between platelet indices and prognosis in HCC. METHOD: A total of 260 patients with HCC between January 2009 and December 2015 were retrospectively analyzed. The optimal platelet distribution width (PDW) cutoff value is identified by the receiver operating characteristic curve (ROC) curve. The relationship between PDW and clinicopathological features was …assessed. The prognostic effects of PDW were assessed by using the Kaplan-Meier method and Cox regression model. RESULT: Elevated PDW level was significantly associated with portal hypertension, vascular invasion, and Child-Pugh grade. In addition, survival curve indicates that patients with high PDW levels have a worse prognosis than patients with low PDW levels (P < 0.001). Multivariate Cox regression analysis identified PDW as an independent factor of prognosis in HCC patients (hazard ratio: 4.460, 95% confidence interval: 2.308–8.619, P < 0.001). CONCLUSION: Elevated PDW may be a novel marker for predicting the prognosis of HCC, but further research is needed to validate our conclusions. Show more

Keywords: Platelet distribution width, hepatocellular carcinoma, prognosis

DOI: 10.3233/CBM-182076

Citation: Cancer Biomarkers, vol. 24, no. 3, pp. 307-313, 2019

Authors: Cymbaluk-Płoska, Aneta | Chudecka-Głaz, Anita | Pius-Sadowska, Ewa | Machaliński, Bogusław | Sompolska-Rzechuła, Agnieszka | Kwiatkowski, Sebastian | Menkiszak, Janusz

Article Type: Research Article

Abstract: BACKGROUND: Endometrial cancer is one of the most common tumor of the woman genital organs. OBJECTIVE: The goal of this study was to determine the lipocalin-2 levels in patients with endometrial cancer compared to those with normal endometrium or mild endometrial pathologies. METHODS: Study included 123 patients with BMI > 21 kg/m 2 who were admitted due to abnormal bleeding, in which 52 patients with endometrial cancer. The NGAL, CA125, HE4 serum levels were determined for all patients. RESULTS: Significantly lower median NGAL serum levels …were found in a group of patients with normal endometrium compared to the endometrial cancer group, p = 0.006. NGAL protein area under ROC curves value as a diagnostic test, differentiating between endometrial cancer and other benign changes endometrium is AUC – 0.81 (p < 0.00001). The NGAL protein had a high sensitivity in all patients included in the analysis: 84% vs. 82% in pre-menopausal patients, and 81% in postmenopausal women with a specificity of 78%, 80% and 87%, respectively. The independent variable for FIGO and model logistic regression proves that NGAL is statistically significant (p = 0.000602), the odds ratio is 3.66. The model for grading shows, that NGAL increase by one ng/ml increases risk chances by 2.32 times in diagnosis with less cancer differentiation. CONCLUSIONS: Our preliminary studies demonstrate that lipocalin-2 may be of value in the diagnostics of uterine body cancers. Show more

Keywords: Lipocalin-2, CA125, HE4, benign endometrial changes, endometrial cancer

DOI: 10.3233/CBM-181942

Citation: Cancer Biomarkers, vol. 24, no. 3, pp. 315-324, 2019

Authors: Jiang, Lihua | lv, Lianhui | Liu, Xinxin | Jiang, Xianqin | Yin, Qiang | Hao, Yuli | Xiao, Lei

Article Type: Research Article

Abstract: Abnormally expressed microRNAs (miRNAs) contribute widely to human cancer, including oral squamous cell carcinoma (OSCC), by regulating their downstream targets. MiR-223 has been proved to be up-regulated in both gastric cancer and ovarian cancer. However, the effect of miR-223 on OSCC is still unclear. Here, we showed that miR-223 was over-expressed in OSCC tissues using qRT-PCR. Next, we investigated the biological mechanism of miR-223 in OSCC. The results demonstrated that miR-223 facilitated the cell proliferation and migration of OSCC using MTT assay and Transwell assay. Furthermore, we stated that the FBXW7 expression was decreased in OSCC and re-expression of FBXW7 …inhibited the proliferation and migration of OSCC. In addition, FBXW7 mimic inversed the promotion effect of miR-223 in regulating of OSCC cells. In short, miR-223 promoted OSCC cell proliferation and migration by downregulating FBXW7, which provided a novel therapeutic strategy for OSCC. Show more

Keywords: MiR-223, OSCC, proliferation, migration, FBXW7

DOI: 10.3233/CBM-181877

Citation: Cancer Biomarkers, vol. 24, no. 3, pp. 325-334, 2019

Authors: Kim, Sung Hyun | Lee, Min Jung | Hwang, Ho Kyung | Lee, Sung Hwan | Kim, Hoguen | Paik, Young-Ki | Kang, Chang Moo

Article Type: Research Article

Abstract: BACKGROUND: For patients with pancreatic cancer, a preoperative assessment of prognosis is crucial to predict cancer recurrence and to prepare a postoperative adjuvant strategy and appropriate patient-counsel. OBJECTIVE: We evaluated the prognostic predictive power of complement factor B (CFB) by comparing it to that of other known tumor markers in resected pancreatic cancer patients. METHODS: From 2012 to 2013 period, we retrospectively reviewed the plasma CFB levels of 35 pancreatic cancer patients. The patients were divided into two groups according to serologic CFB values. Disease-free survival (DFS) and overall survival (OS) rates were …analyzed. RESULTS: Based on the cut-off values of plasma CFB, 15 patients were placed in the low CFB group and the other 20 patients were placed in the high CFB group. There was a significant difference in DFS between the two groups (Low CFB vs. High CFB: 36.9 months vs. 13.9 months, p : 0.007). In the OS analysis, there was also a significant difference in the survival rates of the two groups (Low CFB vs. High CFB: 49.7 months vs. 29.0 months, p : 0.048). CONCLUSION: Preoperative plasma CFB can be used to predict the prognosis of resectable pancreatic cancers; it outperforms both CA 19-9 and CEA. Show more

Keywords: Biomarker, complement factor B, pancreatic cancer, prognosis, survival

DOI: 10.3233/CBM-181847

Citation: Cancer Biomarkers, vol. 24, no. 3, pp. 335-342, 2019

Authors: Chen, Juhui | Zhang, Jingshi | Hong, Liang | Zhou, Yongtao

Article Type: Research Article

Abstract: EGFLAM as a novel gene biomarker has been reported in some cancers but not glioblastoma (GBM) yet. To clarify the functional role of EGFLAM in GBM, we performed this study. Firstly, based on TCGA and Oncomine database, EGFLAM expression and clinical significance in GBM patients was analyzed. Furthermore, the biological effect of EGFLAM in GBM cells was determined by qRT-PCR, CCK-8 assay, colony formation assay, wound healing assay, transwell assays and western blot analysis. The databases analysis showed that EGFLAM expression was at higher levels in GBM patients with poor prognosis. The results indicated that …EGFLAM silence inhibited the proliferation, migration and invasion of U87 cells, which was regulated through repression of PI3K/AKT pathway. Accordingly, the data from our work shed some light on EGFLAM might be a prognostic biomarker and therapeutic target for GBM. Show more

Keywords: EGFLAM, glioblastoma, prognosis, proliferation, PI3K, AKT

DOI: 10.3233/CBM-181740

Citation: Cancer Biomarkers, vol. 24, no. 3, pp. 343-350, 2019

Authors: Krawczyk, Malgorzata A. | Karpinsky, Gabrielle | Izycka-Swieszewska, Ewa | Gabrych, Anna | Kunc, Michal | Fatyga, Aleksandra | Garstka, Monika | Styczewska, Malgorzata | Sokolewicz, Ewa M. | Szlagatys-Sidorkiewicz, Agnieszka | Kazanowska, Bernarda | Bien, Ewa

Article Type: Research Article

Abstract: BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is rare, aggressive soft tissue sarcoma which may affect children. OBJECTIVE: We aimed to assess prognostic significance of immunohistochemical (IHC) markers, osteopontin, fibronectin, survivin, cyclin D1 and p53, in pediatric MPNST. METHODS: A total of 26 pediatric MPNST patients were enrolled in the current study with a median follow-up of 51 months. IHC staining using commercially available monoclonal antibodies were employed to detect analyzed antigens on tissue microarrays. Eventually, all markers were subclassified to high (H) and low (L) expression categories in all analyzed tumors. …RESULTS: High IHC expressions of survivin, cyclin D1, osteopontin, fibronectin, and p53 were detected in 18 (69.2%), 13 (50%), 16 (61.5%), 16 (61.5%), and 13 (50%) tumors, respectively. A significant correlation was demonstrated between cyclin D1 and osteopontin (p = 0.004). Both markers were associated with neurofibromatosis type 1 (NF1) status (p = 0.041 and p = 0.037, respectively). H-fibronectin was more prevalent in deeply located tumors (p = 0.046). None of the markers was associated with IRS stage, age at diagnosis, and tumor size. Univariate analysis identified IRS stage, regional lymph node metastases, NF1, and cyclin D1 as variables associated with overall survival (OS), whereas tumor depth, osteopontin, and cyclin D1 – for relapse-free survival (RFS). Subsequent multivariate analysis identified cyclin D1 and p53 as independent variables predicting RFS, whereas cyclin D1 and regional lymph nodes status were independent predictors for OS. Show more

DOI: 10.3233/CBM-181572

Citation: Cancer Biomarkers, vol. 24, no. 3, pp. 351-361, 2019

Authors: Zou, Shitao | Xu, Yan | Chen, Xingxing | He, Chao | Gao, Aidi | Zhou, Jundong | Chen, Yihong

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: Dysregulation of DNA polymerase iota (Pol ι ) in breast cancer might contribute to the accumulation of genomic mutations and promotes breast cancer progression. In this study we explored the clinical relevance and biological function of Pol ι in breast cancer. METHODS: qRT-PCR was used to determine the expression levels of Pol ι in 31 breast cancer tissues. Then the stable overexpression of Pol ι and knockdown of Pol ι breast cancer cell lines were constructed. Wound-healing assay and …transwell assay were performed to evaluate cell migratory and invasiveness, respectively. Signaling pathway was analyzed by western blot. RESULTS: The expression levels of Pol ι is overexpressed in breast cancer tissues and significantly higher in breast cancer tissues with lymph node metastasis compared to those without lymph node metastasis. Elevated Pol ι expression promoted migratory and invasiveness of breast cancer cells. Signaling pathway analysis indicated EGFR-ERK cascade works as a mediator of Pol ι -induced EMT of breast cancer cells. CONCLUSIONS: These data demonstrate the underlying mechanism by which Pol ι promotes breast cancer progression, suggesting that Pol ι may be a potential therapeutic target against breast cancer. Show more

Keywords: Breast cancer, Pol ι, metastasis, EMT, EGFR

DOI: 10.3233/CBM-181516

Citation: Cancer Biomarkers, vol. 24, no. 3, pp. 363-370, 2019

Authors: Bai, Yuquan | Xiong, Lecai | Zhu, Minglin | Yang, Zetian | Zhao, Jinping | Tang, Hexiao

Article Type: Research Article

Abstract: Lung cancer is a malignant tumor with high morbidity and mortality, of which 80% is non-small cell lung cancer (NSCLC). And lung adenocarcinoma (LUAD) is the most important and common subtype in the NSCLC. In current study, the microarray data GSE31210 containing LUAD (n = 226) and normal lung tissue (n = 20) was analyzed to identify 965 differentially expressed genes, on which weighted gene co-expression network analysis was performed. Finally, it was confirmed that there was a significant correlation between brown module and LUAD stage. In the significant module, …a total of 54 network hub genes were identified, and six of them were also identified as hub genes of the protein-protein interaction network. In validation, KIF2C showed a higher correlation with disease stage than other hub genes (p < 0.001, R2 = 0.955). Functional enrichment suggests that KIF2C is associated with cell mitosis and cell cycle. Combined with clinicopathological parameters, we found that the high expression of KIF2C is closely related to the relapse and tumor stage of LUAD. Survival analysis showed a significant reduction in overall survival in LUAD patients with high expression of KIF2C. Gene set enrichment analysis (GSEA) also showed that the “cell cycle signaling pathway” and “P53 related pathway” were significantly enriched in LUAD samples with high expression of KIF2C (FDR < 0.05). In conclusion, based on the co-expression analysis, KIF2C was identified in the association with progression and prognosis of LUAD, which might refer a poor prognosis probably by regulating cell cycle signaling pathway. Show more

Keywords: KIF2C, Lung adenocarcinoma, co-expression analysis, cell cycle

DOI: 10.3233/CBM-181512

Citation: Cancer Biomarkers, vol. 24, no. 3, pp. 371-382, 2019